Ischemia/reperfusion injury(I/RI) is the major cause of acute renal failure and delayed graft function(DGF) unavoidable in renal transplantation. Enormous studies on ischemia damage playing a role in activating graft rejection factors, such as T cells or macrophages, are being reported. Present study was performed to determine whether ischemia time would play an important role in activating rejection-related factors or not in rat models of I/RI. Male Sprague-Dawley rats were submitted to 30, 45, and 60 minutes of warm renal ischemia with nephrectomy or control animals underwent sham operation(unilateral nephrectomy). Renal function and survival rates were evaluated on day 0, 1, 2, 3, 5 and 7. Immunofluorescence staining of dendritic cells(DCs), natural killer(NK) cells, macrophages, B cells, CD4+ and CD8+ T cells were measured on day 1 and 7 after renal I/RI. Survival rates dropped below 50% after day 3 in 45 minutes ischemia. Histologic analysis of ischemic kidneys revealed a significant loss of tubular architecture and infiltration of inflammatory cells. DCs, NK cells, macrophages, CD4+ and CD8+ T cells were infiltrated from a day after I/RI depending on ischemia time. Antigen presenting cells(DCs, NK cells or macrophages) and even T cells were infiltrated 24 hours post-I/RI, which is at the time of acute tubular necrosis. During the regeneration phase, not only these cells increased but B cells also appeared in more than 45 minutes ischemia. The numbers of the innate and the adaptive immune cells increased depending on ischemia as well as reperfusion time. These changes of infiltrating cells resulting from each I/RI model show that ischemic time plays a role in activating rejection related immune factors and have consequences on progression of renal disease in transplanted and native kidneys.
Lee Ji-Suk;Rho Kwang-Sik;Kim Ji-Hong;Lee Jae-Seung;Kim Pyung-Kil
Childhood Kidney Diseases
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v.1
no.2
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pp.144-150
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1997
Purpose : The kidney is one of the most common sites of cyst formation. Cystic diseases of the kidney are a diverse group of clinicopathologic entities and variable prognosis. They span a wide range of both age of presentation and severity of the renal disease. And many of them are systemic disorders, sharing similar process of cyst formation in other organs. Recently, development of imaging studies has been contributing widely to the diagnosis of the diseases. Treatment, however, is not established satisfactorily. We performed this study to evaluate the occurrence and treatment of cystic diseases of the kidney. Methods : We reviewed retrospectively the medical records of 44 patients with cystic diseases of the kidney in the Department of Pediatrics, during last 11 years. Results : In the 44 patients with cystic diseases of the kidney, 31 patients(71%) had multicystic dysplastic kidney and 11(35%) of them received nephrectomy due to differentiation from neoplasms or severe abdominal distension. Seven patients(16%) had polycystic kidney disease, and all of them were infantile type. Five patients(11%) were diagnosed as having a simple renal cysts. Progression to renal failure was noted in none of the cases. In 14(32%) out of total 44 patients, the diagnosis was made in neonatal or infantile pelted. Conclusion : The incidence of cystic diseases of the kidney appeared very low, but further investigation on their pathogenesis, classification, and indication of treatment is needed.
Purpose : Henoch-$Sch{\ddot{o}}nlein$ purpura(HSP) is a common pediatric discase presenting most frequently with skin, gastrointestinal, joint and renal manifestations. The prognosis of HSP is mainly determined by the involvement of the kidney, but prognostic markers have not been established. We evaluated the patients who have HSP nephritis with nephrotic syndrome. Method : Clinical manifestations and laboratory findings were observed and analyzed in 34 cases with HSP which were manifested by nephrotic syndrome hospitalized at Kyung Hee university Hospital during the period from Jan. 1990 to Dec. 1998. Results : 1) Male to female ratio was 1.3:1, and mean age at onset was 8.3 year. 2) Mean duration from symptom onset to renal biopsy was 10.5 weeks. 3) Proportion of patients presenting with acute nephritis was 32.4$\%$, gross hematuria 17.6$\%$, microscopic hematuria 50$\%$. 4) The findings of renal biopsy were 20 cases of grade II, 11 cases of grade III, 2 cases of grade I, 1 case of grade IV according to classification by ISKDC. 5) Patients with grade I were recovered with no residual defect, but patients with grade IV shows active renal disease(states C). Conclusion : Among the 디le patients with Henoch-$Sch{\ddot{o}}nlein$ purpura accompanying nephrotic syndrome, more aggressive treatment might be needed in patients showing crescents formation on renal biopsy. A prospective study will be needed to explore the progression of this disease.
Kim, Khi-Joo;Kim, Joung-A;Shin, Jae-Il;Hwang, You-Sik;Cheung, Il-Chun;Lim, Jong-Baeck;Lee, Jae-Seung
Childhood Kidney Diseases
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v.11
no.2
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pp.161-167
/
2007
Purpose : GFR(glomerular filtration rate) is a fundamental parameter in detecting renal impairment and predicts the progression of renal disease. Because serum creatinine has several disadvantages, serum cystatin C has been recently proposed as a new endogenous marker for GFR. We compared serum cystatin C with creatinine and creatinine clearance to investigate the clinical usefulness of cystatin C. Methods : We retrospectively analyzed 46 patients(60 case numbers) who had various renal diseases and classified them into 3 groups according to creatinine clearance(Group 1 : CrCl <40 mL/min/$1.73m^2$, Group 2 : CrCl 40-60 mL/min/$1.73m^2$, Group 3 CrCl >60 mL/min/$1.73m^2$). We measured serum creatinine, cystatin C and creatinine clearance and also analyzed the correlations among them. Results : Serum cystatin C and creatinine showed a similar correlation to creatinine clearance (r=0.685, r=0.640, respectively) and showed similar diagnostic accuracy in detecting decreased GFR(AUC, cystatin C 0.829 vs. creatinine 0.826, P=0.848). Serum cystatin C showed a greater sensitivity for detecting a decreased GFR than creatinine in Group 2 and 3(Group 1 : 100% vs. 100%, Group 2 : 70% vs. 35%, Group 3 : 46% vs. 15%). Conclusions : Serum cystatin C could be a useful endogenous marker for GFR and would be superior to serum creatinine in early detection of renal impairment in pediatric patients with renal diseases.
Purpose : Continuous renal replacement therapy(CRRT) has been the first choice for the treatment of acute renal failure in critically ill children not only in western countries but also in Korea. However, there are very few studies that have analyzed the outcome and prognosis of this modality in Korean children. We performed this study to evaluate the factors associated with the outcome and prognosis of patients treated with CRRT. Methods : We retrospectively reviewed the medical records of 32 children who had received CRRT at Severance hospital from 2003 to 2006. The mean age was 7.5 years(range 4 days-16 years) and the mean body weight was 25.8 kg (range 3.2-63 kg). Results : Eleven(34.4%) of the 32 patients survived. Bone marrow transplantation and malignancy were the most common causes of death and underlying disease leading to the need for CRRT Mean patient weight, age, duration of CRRT, number of organ failures, urine output, estimated glomerular filtration rate(eGFR), C-reactive protein, and blood urea level did not differ significantly between survivors and nonsurvivors. (1) Pediatric risk of mortality(PRISM) III score at CRRT initiation($9.8{\pm}5.3$ vs. $26.7{\pm}7.6$, P<0.0001), (2) maximum pressor number ($2.1{\pm}1.2$ vs. $3.0{\pm}1.0$, P=0.038), and (3) the degree of fluid overload($5.2{\pm}6.0$ vs. $15.0{\pm}8.9$, P=0.002) were significantly lower in survivers than in nonsurvivors. Multivariate analysis revealed that fluid overload was the only independent factor reducing survival rate. Conclusion : CRRT was successfully applied to the treatment of acute renal failure in a wide range of critically ill children. To improve survival, we suggest the early initiation of CRRT to prevent the systemic worsening and progression of fluid overload in critically ill children with acute renal failure. (J Korean Soc Pediatr Nephrol 2007;11:247-254)
Purpose : The progressive deterioration of renal function in children can impose a serious and lifelong impact on their lives. The ultimate goal in the management of children with chronic kidney disease(CKD) is to prolong survival, to prevent complications, and to promote growth and neurodevelopment. The aim of this study is to investigate the risk factors for the decline of renal function in pediatric CKD patients. Methods : Data from patients who met the criteria for the Kidney Disease Outcomes Quality Initiative(K/DOQI) CKD stage 2 to 4 between August 1999 and March 2007 were retrospectively analyzed. The estimated glomerular filtration rate(eGFR) was calculated by the Schwartz formula, using serum creatinine levels and height. We calculated the annual eGFR change from the difference between the baseline eGFR and the last eGFR divided by the duration(years) of the follow-up period. We analyzed the association between the annual eGFR change and factors such as age, gender, K/DOQI stage, underlying renal disease, serum calcium, and inorganic phosphorous during the follow-up period. Results : Sixty one children(44 boys & 17 girls) were enrolled. The age at entry was $7.1{\pm}4.7$ years. The annual eGFR change was $-1.2{\pm}11.9 mL/min/1.73m^2/year$. Our study showed that older age(P=0.005). hypocalcemia(P=0.012), and hypenhosphatemia(P=0.002) were significantly related to more rapid decline in renal function. Conclusion : In pediatric CKD, older age, hypocalcemia and hyperphosphatemia are related to more rapid deterioration of renal function.
Purpose: The present study is an investigation of the progression and prognosis of acute intrinsic renal failure in neonates and children with a diagnosis of acute renal failure or other diseases on admission. Methods: This research is based on a retrospective analysis conducted on 59 patients(male: female=2.2:1) diagnosed with acute intrinsic renal failure between January 2000 and June 2006 at Busan Paik Hospital. The clinical diagnostic criteria of acute renal failure used was serum creatinine <1.2 mg/dL, oliguria with urine output$\leq$0.5 mL/kg/hr and anuria with urine output <50 mL per day. Results: Among those placed under investigation, 7 patients were neonates, 10 patients were 2 months-2 years old, 12 patients were 3-6 years old, 21 patients were 7-12 years old and 9 patients were 13-16 years old. It took 3.1${\pm}$2.8 days on average until the diagnosis was made. The urine output distribution was 21 persons for the oliguria group, and 36 persons for the non-oliguria group, and 2 persons for the anuria group. For the underlying causes, 30 persons were classified in the primary renal disease group, 14 persons in the infection group, 9 persons in the malignancy group, and 6 persons were categorized in another group. As for age distribution, the infected group was predominantly neonates, whereas the dominant age ranges for the primary renal disease and infection categories were 2 months to 2 years old. Also, the primary renal disease was dominant among older children, aged 3 and up. No difference was detected according to seasonal prevalence. However, there was a high morbidity rate among hemolytic uremic syndrome diagnosed in the summer. Peritoneal dialysis was used to treat 4 patients. It took 10.0${\pm}$6.7 days until the patients improved. 18 patients died. The non-oliguria group's mortality rate was lower than other groups. There was a high mortality rate in the neonates and malignancy group. Conclusion: Acute renal failure in childhood seems to take a better clinical course than in adulthood when there is an early diagnosis and proper treatment of underlying diseases.
Mitotic centromere-associated kinesin (MCAK), which is a member of the Kin I (internal motor domain) subfamily of kinesin-related proteins, is known to play a role in mitotic segregation of chromosome during M phase of the cell cycle. In the present study, we have produced a rat polyclonal antibody using human MCAK (HsMCAK) expressed in E. coli as the antigen. The antibody specifically recognized the HsMCAK protein (81 kDa), and could detect its nuclear localization in human Jurkat T cells and 293T cells by Western blot analysis. The specific stage of the cell cycle was obtained through blocking by either hydroxyl urea or nocodazole and subsequent releasing from each blocking for 2, 4, and 7 h. While the protein level of HsMCAK reached a maximum level in the S phase with slight decline in the $G_{2}-M$ phase, the electrophoretic mobility shift from $p81^{MCAK}\;to\;p84^{MCAK}$ began to be induced in the late S phase and reached a maximum level in the $G_{2}/M $ phase, and then it disappeared as the cells enter into the $G_{1}$ phase. Immunocytochemical analysis revealed that HsMCAK protein localized to centrosome and nucleus at the interphase, whereas it appeared to localize to the spindle pole, centromere of the condensed mitotic DNA, spindle fiber, or midbody, depending on the specific stage of the M phase. These results demonstrate that a rat polyclonal antibody raised against recombinant HsMCAK expressed in E. coli specifically detects human MCAK, and indicate that the electrophoretic mobility shift from $p81^{MCAK}\;to\;p84^{MCAK}$, which may be associated with its differential intracellular localization during the cell cycle, fluctuates with a maximum level of the shift at the $G_{2}-M$ phase.
Background: Patch angioplasty is an alternative surgical procedure to coronary artery bypass grafting (CABG) for left main coronary ostial stenosis. The purpose of this study is to evaluate the outcome of patch angioplasty by analyzing the short-term and long-term results. Material and Method: Twenty nine patients who had undergone patch angioplasty due to left main coronary ostial stenosis between July 1991 and May 2003 were enrolled in the study. The mean age of the patients was 53.1 $\pm$12.5 years. There were 8 males and 21 females, and there were 12 female patients who had no risk factor for atherosclerosis. Twenty six (89.7%) patients showed isolated coronary ostial stenosis without any distal coronary lesion. Result: Anterior approach was used in 28 patients and superior approach was used in one patient. Transsection of the main pulmonary artery was used in one patient. Concomitant CABG was performed in 4 patients because of left anterior descending artery lesions in 3 patients and unstable postoperative hemodynamic status in one patient. Hospital mortality had occurred in one patient (3.4%) and late mortality also in one patient, therefore the overall 5 year survival rate was 91.2$\pm$6.1%. Seventeen coronary angiographies were done in 13 patients (44.8%) postoperatively. Two distal patch stenoses, 1 proximal patch stenosis, and 1 new right coronary ostial lesion were identified and 3 percutaneous interventions and 1 CABG were performed during the follow-up period. The overall 5 year freedom from reintervention rate was 82.4 $\pm$ 8.5%. Aortic regurgitation less than grade 1 had developed postoperatively in 4 patients and one patient showed progression of preexisting aortic regurgitation from grade II to III. Conclusion: Patch angioplasty in left main coronary ostial lesion showed acceptable short-term and long-term results in this study. However, restenosis at the patch anastomosis site and aortic regurgitation should be carefully investigated during the follow-up period.
Lee, Hyun Ah;Kim, Ji Eun;Choi, Jun Young;Sung, Ji Eun;Youn, Woo Bin;Son, Hong Joo;Lee, Hee Seob;Kang, Hyun-Gu;Hwang, Dae Youn
Journal of Life Science
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v.30
no.4
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pp.331-342
/
2020
The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.
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